Annual Review of Cancer Biology - Volume 2, 2018

A great deal of interest has developed around evidence of a role for or a marker of extracellular vesicles (EVs)/exosomes and metastatic cancer. However, the strength of a functional connection between EVs and cancer has been hampered by inadequate characterization of EVs and a lack of mechanistic details describing the means by which molecular constituents are incorporated into target cells. Here we consider the mechanisms by which EVs may mediate intercellular communication through ligand-receptor interactions or membrane fusion at the surface of or within recipient cells. We highlight common pitfalls in EV purification procedures and describe how multistep methods combined with quantitative evaluation of EV purification are critical for attributing functional effects to EVs. We explain current limitations in our understanding of the functional internalization of EVs and discuss relevant biological and biochemical controls that may be applied to help strengthen the case for a meaningful effect on target cells.

The genomics-era search for cancer-causing mutations has identified subunits of SWI/SNF (BAF) chromatin remodeling complexes as major targets of mutation. The mechanism by which mutations in SWI/SNF complexes might drive cancer has become the subject of debate, as these complexes have roles in both transcriptional regulation and maintenance of genomic integrity. Recent discoveries now reveal that SWI/SNF complexes broadly control the activity of transcriptional enhancers to regulate lineage-specific differentiation. Here, we synthesize an integrative model of SWI/SNF complex function, identifying perturbed control of enhancer activity as the central mechanism underlying tumor suppression and highlighting how this yields new opportunities for therapeutic intervention.

The basic catalog of DNA-based alterations that contribute to the onset and progression of cancer has been largely elucidated due to the results obtained from the combination of massively parallel sequencing and computational analysis methods applied to thousands of cancer samples. These combined approaches have provided novel and surprising insights into the myriad ways that DNA-level disruptions lead to activation and inactivation of cellular pathways, thereby altering the carefully controlled growth and division of normal cells and rendering them cancerous. This review presents genomic insights gained from these large-scale studies and highlights how this new knowledge will be translated in the future into improved clinical care and monitoring of cancer patients.